scholarly journals Neoadjuvant/Perioperative Treatment Affects Spatial Distribution and Densities of Tumor Associated Neutrophils and CD8+ Lymphocytes in Gastric Cancer

2021 ◽  
Vol 11 (11) ◽  
pp. 1184
Author(s):  
Anne Hoffmann ◽  
Hans-Michael Behrens ◽  
Steffen Heckl ◽  
Sandra Krüger ◽  
Thomas Becker ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Regression ◽  
Cytotoxic T Cells ◽  
Biological Significance ◽  
Patient Characteristics ◽  
Historical Cohort ◽  
Invasion Front ◽  
Tumor Center ◽  
Treatment Naïve ◽  
Tumor Associated Neutrophils

Tumor associated neutrophils (TANs) and cytotoxic T cells (CTLs) are part of the tumor microenvironment of gastric cancer (GC). We explored their tumor biological significance in neoadjuvantly/perioperatively treated GC. Immunostaining was performed on whole tissue sections of 173 GCs, using antibodies directed against myeloperoxidase (MPO) and CD8. Stained specimens were digitalized, and the densities of TANs and CTLs were assessed separately in the mucosa, tumor surface, tumor center, invasion front, and tumor scar. The densities were correlated with clinicopathological patient characteristics. Compared with a historical cohort of 449 treatment naive GCs, the TAN density in the invasion front was significantly lower in neoadjuvantly/perioperatively treated GCs. TAN density in the tumor center and invasion front correlated with tumor regression. TAN density also correlated with CTL density in the tumor center and invasion front. A high density of CTL in the tumor center correlated with an improved overall survival and tumor specific survival. We show that neoadjuvant/perioperative (radio-) chemotherapy impacts on the immune microenvironment of GC, while also depending on sex. The density of TANs in neoadjuvantly/perioperatively treated GCs differed from findings made in a treatment naive GC cohort.

scholarly journals Sexual dimorphism in gastric cancer: tumor-associated neutrophils predict patient outcome only for women

2019 ◽  
Vol 146 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Franziska Clausen ◽  
Hans-Michael Behrens ◽  
Sandra Krüger ◽  
Christoph Röcken
Keyword(s):  
Gastric Cancer ◽  
Patient Outcome ◽  
Sexual Dimorphism ◽  
Biological Significance ◽  
Tumor Grade ◽  
Distribution Patterns ◽  
Patient Characteristics ◽  
Invasion Front ◽  
Tumor Center ◽  
Tumor Associated Neutrophils

Abstract Purpose Tumor-associated neutrophils (TANs) are part of the tumor immune microenvironment (TIME) and may contribute to gastric cancer (GC) biology. We hypothesized that TAN are enriched in the TIME, show sex-specific differences, and correlate with patient outcome. Methods We analyzed the distribution and putative tumor biological significance of TANs in a well-characterized, therapy-naïve, European GC cohort using immunohistochemical staining of myeloperoxidase (MPO), and digital image analysis using Definiens Tissue Studio®. Results Different tumor compartments were examined, and TAN densities were correlated with various clinicopathological patient characteristics. TAN density showed a large interindividual variability ranging from 0 to 6711.0 TANs/mm2. Intratumoral distribution patterns were inhomogeneous (tumor surface vs. tumor center vs. invasion front) and correlated significantly with Laurén phenotype, tumor grade, and microsatellite status in the tumor center and invasion front. In the multivariate analysis, TAN density in the invasion front was an independent predictor of tumor-specific survival only for women (HR = 2.77, p   < 0.001). In men, no correlation was found between TAN density and survival. Conclusion With regard to TANs, our study independently validates sexual dimorphism in GC biology.

scholarly journals Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF

2016 ◽  
Vol 113 (40) ◽  
pp. 11300-11305 ◽  
Author(s):  
Tsuguhide Takeshima ◽  
Laurentiu M. Pop ◽  
Aaron Laine ◽  
Puneeth Iyengar ◽  
Ellen S. Vitetta ◽  
...  
Keyword(s):  
Tumor Regression ◽  
Cytotoxic T Cells ◽  
Sterile Inflammation ◽  
Clinical Settings ◽  
Mouse Tumor ◽  
Concurrent Administration ◽  
Immunological Effects ◽  
Radiation Induced ◽  
Induced Apoptosis ◽  
Tumor Associated Neutrophils

Radiation therapy (RT), a major modality for treating localized tumors, can induce tumor regression outside the radiation field through an abscopal effect that is thought to involve the immune system. Our studies were designed to understand the early immunological effects of RT in the tumor microenvironment using several syngeneic mouse tumor models. We observed that RT induced sterile inflammation with a rapid and transient infiltration of CD11b+Gr-1high+ neutrophils into the tumors. RT-recruited tumor-associated neutrophils (RT-Ns) exhibited an increased production of reactive oxygen species and induced apoptosis of tumor cells. Tumor infiltration of RT-Ns resulted in sterile inflammation and, eventually, the activation of tumor-specific cytotoxic T cells, their recruitment into the tumor site, and tumor regression. Finally, the concurrent administration of granulocyte colony-stimulating factor (G-CSF) enhanced RT-mediated antitumor activity by activating RT-Ns. Our results suggest that the combination of RT and G-CSF should be further evaluated in preclinical and clinical settings.

Ultrastructural Localization Study of Carcinoembryonic Antigen (CEA) in Gastric Cancer: Immunoelectron Microscopic Observation

1990 ◽  
Vol 48 (3) ◽  
pp. 252-253
Author(s):  
Dong Yuming ◽  
Yang Guanglin ◽  
Wu Jifeng ◽  
Chen Xiaolin
Keyword(s):  
Gastric Cancer ◽  
Intestinal Metaplasia ◽  
Cancer Cells ◽  
Microscopic Observation ◽  
Biological Significance ◽  
Ultrastructural Localization ◽  
Mucinous Carcinoma ◽  
Surface Glycoprotein ◽  
Tubular Adenocarcinoma ◽  
Pap Method

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.

scholarly journals Bioinformatics analysis of the prognosis and biological significance of VCAN in gastric cancer

2021 ◽  
Author(s):  
Xiao‐yan Huang ◽  
Jin‐jian Liu ◽  
Xiong Liu ◽  
Yao‐hui Wang ◽  
Wei Xiang
Keyword(s):  
Gastric Cancer ◽  
Bioinformatics Analysis ◽  
Biological Significance

scholarly journals Body Composition Changes in Gastric Cancer Patients during Preoperative FLOT Therapy: Preliminary Results of an Italian Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 960
Author(s):  
Emanuele Rinninella ◽  
Antonia Strippoli ◽  
Marco Cintoni ◽  
Pauline Raoul ◽  
Raffaella Vivolo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Body Composition ◽  
Tumor Regression ◽  
Evaluation Criteria ◽  
Tumor Regression Grade ◽  
Skeletal Muscle Index ◽  
Before And After ◽  
Gastric Cancer Patients ◽  
The Impact ◽  
Composition Changes

Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.

scholarly journals Melan-A–specific Cytotoxic T Cells Are Associated with Tumor Regression and Autoimmunity Following Treatment with Anti-CTLA-4

2009 ◽  
Vol 15 (7) ◽  
pp. 2507-2513 ◽  
Author(s):  
Oliver Klein ◽  
Lisa M. Ebert ◽  
Theo Nicholaou ◽  
Judy Browning ◽  
Sarah E. Russell ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Regression ◽  
Cytotoxic T Cells

scholarly journals Expression and biological significance of human kallikrein 6 in gastric cancer tissues

2013 ◽  
Vol 1 ◽  
pp. 64-67
Author(s):  
Cheng Jin Hu ◽  
Kui Xiang Chen ◽  
Jin Feng Zheng ◽  
Ying Jian Chen
Keyword(s):  
Gastric Cancer ◽  
Biological Significance ◽  
Cancer Tissues ◽  
Kallikrein 6

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Biological Significance ◽  
High Expression ◽  
Cancer Tissue ◽  
Cox Regression Analysis ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.

scholarly journals Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 407 ◽  
Author(s):  
Emily Hays ◽  
Benjamin Bonavida
Keyword(s):  
Nitric Oxide ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Tumor Regression ◽  
Cytotoxic T Cells ◽  
Resistance Mechanisms ◽  
Binding Activity ◽  
No Donors ◽  
Dna Binding Activity ◽  
Immune Resistance

In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in a subset of patients, another subset remained unresponsive initially, or became resistant to further therapies. Hence, there is a need to develop novel approaches to treat those unresponsive patients. Several investigations have been reported to explain the underlying mechanisms of immune resistance, including the anti-proliferative and anti-apoptotic pathways and, in addition, the increased expression of the transcription factor Yin-Yang 1 (YY1) and the programmed death ligand 1 (PD-L1). We have reported that YY1 leads to immune resistance through increasing HIF-1α accumulation and PD-L1 expression. These mechanisms inhibit the ability of the cytotoxic T-lymphocytes to mediate their cytotoxic functions via the inhibitory signal delivered by the PD-L1 on tumor cells to the PD-1 receptor on cytotoxic T-cells. Thus, means to override these resistance mechanisms are needed to sensitize the tumor cells to both cell killing and inhibition of tumor progression. Treatment with nitric oxide (NO) donors has been shown to sensitize many types of tumors to chemotherapy, immunotherapy, and radiotherapy. Treatment of cancer cell lines with NO donors has resulted in the inhibition of cancer cell activities via, in part, the inhibition of YY1 and PD-L1. The NO-mediated inhibition of YY1 was the result of both the inhibition of the upstream NF-κB pathway as well as the S-nitrosylation of YY1, leading to both the downregulation of YY1 expression as well as the inhibition of YY1-DNA binding activity, respectively. Also, treatment with NO donors induced the inhibition of YY1 and resulted in the inhibition of PD-L1 expression. Based on the above findings, we propose that treatment of tumor cells with the combination of NO donors, at optimal noncytotoxic doses, and anti-tumor cytotoxic effector cells or other conventional therapies will result in a synergistic anticancer activity and tumor regression.

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